Dental Caries Dental Caries Demineralization of by ert554898

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									Dental Caries
Demineralization of the tooth surface
       caused by bacteria
       Chemicoparasitic theory (1890)

● Proposed in 1890 by W. D. Miller in his book "The
   microorganisms of the human mouth" based upon the work
   done in Robert Koch’s laboratory in Berlin
● Acid and parasite
● Showed that the degradation of carbohydrate-containing foods
   resulted in acid formation and was able to demonstrate this
   process in vitro with isolated oral bacteria and extracted teeth.
● Concluded that dental caries was caused by multiple species of
   oral bacteria
● No specific bacteria was implicated – “non-specific”

● Dental caries was caused by multiple or all species of
  oral bacteria “Non-specific plaque hypothesis„

● Proper prevention is therefore is to remove or
  minimize multiple bacterial species.

 Practice of tooth brushing, flossing and professional
  The specific plaque hypothesis and
             dental caries
● In 1924, Clark isolated streptococci from human
   carious lesions, and named Streptococcus mutans

● In 1960, Keyes showed that ‘caries-free’ hamsters
   develop dental caries only when caged together with
   ‘caries-active’ hamsters - Infectious and

● The bacteria previously referred to as S. mutans are
  actually seven distinct species now called mutans
  streptococci (MS)

● MS are the principal etiological agents of dental caries
 Microbial etiology of dental
Mutans Streptococci (MS)
Requires a relatively high proportion (2-10%) of mutans
   streptococci within dental plaque.
Possess adherence activity (to tooth surface)
Produce higher amounts of acid from sugars than other     bacterial
   types, and possess acid tolerance
Produce extracellular polysaccharides from sucrose.

● Lactobacilli
 Dentin, root caries, acidogenic, acid tolerant
● Actinomyces viscosus
 Acidogenic and acid tolerant
      Current diagnosis and
● Future diagnostics using microbiology
      Detection and monitoring of cariogenic bacteria others

● Potential preventive measures based on
  microbiological principle
      Preventing bacteria from colonizing tooth surface
      Local and topical antimicrobial agents
      Replacement therapy
Mutans Streptococci
       Early acquisition and
● Mutans streptococci appear in the mouth after teeth
have erupted as they need solid surfaces to colonize.

● The establishment of the bacteria seems rather slow
the first two years, and one talks about a "window of
infectivity" which would open after about two years.

● There seems to be a family pattern as similar types of
bacteria have been found in the mouth of child and
parents, in particular mothers.
     Mutans Streptococci -
● Global distribution – found in all populations

● High counts - 106/ml saliva

● Usually, serotype c (Streptococcus mutans) is
  the dominating serotype. One person can
  have several serotypes (both Streptococcus
  mutans and Streptococcus sobrinus).
Dental caries in relation to mutans
● Gram-positive bacteria which are commonly isolated from the
   oral cavity.

● Cariogenic, highly acidogenic organisms, however, has low
   affinity for tooth surfaces.

● Associated more with carious dentine and the advancing front of
   caries lesions rather than with the initiation of the disease.

● Usually lactobacilli comprise less than 1% of the total cultivable
   microflora. However, their proportions and prevalence may
   increase at advanced caries lesions both of the enamel and of
   the root surface.
         Sugar metabolism of
          cariogenic bacteria
● Acid production (lactate) from glucose and fructose

● Formation of extracellular polysaccharides (glucose polymer,
   fructose polymer) from the energy of the disaccharide bond of
   sucrose. (glucosyltransferase, fructosyltransferase)

        - Increase the thickness of plaque substantially
        - Changing the chemical nature of its extracellular space from
           liquid to gel.
        - The gel limits movement of some ions, protects the plaque
           biofilm from salivary buffering. Plaque which has not had
            contact with sucrose is both thinner and better buffered.
           The metabolism of S.
● Key to the pathogenesis of dental caries
        - The fermentation of these carbohydrates is the principal
   source         of energy for S. mutans
                Genome sequence shows that S. mutans can metabolize a
                variety of carbohydrates than any other G(+) microorganism
        - The glycolytic pathway leads to the production of
          to lactic acid (by LDH activity), formate, ethanol and
        - The acidic environments are responsible for the damage
           tooth structure
        - Acid tolerant – based on a membrane-bound, acid stable,
           proton-translocating ATPase
    Virulence factors of S.
● Production of acid
     Wall-associated protein A (WapA)
     S. mutans LraI operon (SloC)
     Glucan-binding proteins A and C
●Adherence mechanism
Two methods of attachment

● Sucrose independent –using ionic and lectin like interaction

- Adhere to salivary agglutinin glycoprotein (SpaP:
  Streptococcal protein antigen P, aka antigen I/II)
       - Isogenic mutants of SpaP
       - Passive immunization study

 - Adhere to other bacteria, the extracellular matrix and
   epithelial cell-surface receptors
Two methods of attachment

● Sucrose dependent

     - Adhere to tooth surface by synthesizing glucans by

     - Glucan promotes cell-cell aggregation by interacting with

        surface-associated glucan binding protein
Virulence factors of S.
  Ecological basis of dental
● Environmental changes
  A variety of environmental signals in complex communities

● Ecological shift
 The signal triggers adaptation to acid environment

● Biofilm characteristics
   Virulence properties of S.
● Adhesion, acidogenicity, and acid tolerance

● Each of these properties works coordinately to alter dental plaque

● The ecological changes are characterized by increased
   proportions of S. mutans and other species that are similar
   lacidogenic and aciduric.

● The selection for a cariogenic flora increases the magnitude of
   the drop in pH following the fermentation of available
   carbohydrate and increases the probability of enamel
 Novel approach to dental
caries Replacement therapy
● Replacing a specific bacterial pathogen with a non-
  pathogenic strain, an effector strain
      - should not cause disease itself or disrupt the ecosystem
  to other
           disease state
         - must persistently colonize the host tissue at risk and
           prevent colonization or outgrowth of the pathogen
        - should possess a high degree of genetic stability

● Possible life-long cavity protection
● Little or no risk of side effects
● Minimal patient education and compliance
        Replacement therapy for the
               prevention of
               dental caries
● Lactate dehydrogenase (LDH)-deficient mutants
 Streptococcus rattus LDH mutants were shown to have little or no
  cariogenic potential in vitro and in various rodent models.

● Lantibiotic production
 S. mutans strain (JH1000) produces a lantibiotic called mutacin
  1140 capable of killing virtually all other strains of mutans
  streptococci against which it was tested.

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